BioavailabilityBioavailability

DistributionDistribution

Absorption and TransportAbsorption and Transport

Volume of Distribution

The volume of distribution is given by the following equation:

Therefore the dose required to give a certain plasma concentration can be determined if the VD for that drug is known. The VD is not a physiologic value; it is more a reflection of how a drug will distribute throughout the body depending on several physicochemical properties, e.g. solubility, charge, size, etc.

VD is often calculated per weight of body – it is not volume any more!

Medication Vd / kg body weight

heparin 0.05-0.1

insulin 0.05-0.1

warfarin 0.1-0.2

sulfamethoxazole 0.1-0.2

glibenclamide 0.1-0.2

atenolol 0.1-0.2

NXY-059 0.1-0.2

tubocurarine 0.2-0.4

theophylline 0.4-0.7

ethanol 0.7-0.9

neostigmine 0.7-0.9

phenytoin 0.7-0.9

methotrexate 1-2

indometacin 1-2

paracetamol 1-2

diazepam 1-2

lidocaine 1-2

glyceryl nitrate 2-5

morphine 2-5

propranolol 2-5

digoxin 2-5

chlorpromazine 2-5

nortriptyline 2-5

chloroquine 200

VD Proportion of Drug in body water

0.1 40%0.15 27%1 4%10 0.4%

Two compartment model

Blood Tissue

Mode of entry of drugs/toxins

Skin transport

Respiratory route

Oral route

sintravenou

oral

curveunderarea

curveunderareailitybioavailab

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Organ pH Surface Area Time

Stomach 1-3 up to 5 m2 0.5-20 h

Small Intestine 5-7 200 m2 2 h

Colon 7-8 up to 5 2 h – 1 week

logC

Time

Drug Bioavailability VD (L/kg weight)

Diazepam 100 0.5-2Morphine 15-60 3-5Pentobarbital 95 0.7-10Tetrahydrocannabinol 6 9-11

VD Proportion of Drug in body water0.1 40%0.15 27%1 4%10 0.4%

Surface Area

Diffusion Coefficient

Solubility

Concentration in bulk

Diffusion Layer thickness

Solid

BiLayer Membrane

pH1

pH2

Passive Transport

Hydrophobic area

Aqeous area

Aqeous area